Age and sex drive differential behavioral and neuroimmune phenotypes during postoperative pain

Santos, Natalia Lucia dos; Lenert, Melissa E.; Castillo, Zachary W.; Mody, Prapti H; Thompson, Lucien T.; Burton, Michael D.

doi:10.1016/j.neurobiolaging.2022.09.008

Cited by 7 publications

(5 citation statements)

References 94 publications

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“…However, we found an unexpected female-driven acceleration of mechanical sensitivity. Aged animals can show delayed onset pain-like behaviors 48 which we also detected in our control female animals but not in primed-cell recipient animals (Fig. 7H-I).…”

Section: Transplant Of Neonatal "Primed" Bone Marrow Alters Incision-...supporting

confidence: 71%

“…Recently dos Santos et al found a delayed onset hypersensitivity in aged animals following an incision injury as well as blunted hyperalgesic priming in aged animals. This was connected with changes in inflammation in older rodents compared to younger animals 98 . We found a similar delay following a BMT in female incision at P147, but not in non-BMT males or females.…”

Section: Discussionmentioning

confidence: 89%

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Macrophage epigenetic memories of early life injury drive neonatal nociceptive priming

Dourson

Fadaka

Warshak

et al. 2023

Preprint

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These systems are vulnerable to effects of early life injury which can influence outcomes related to nociception following subsequent injury later in life (i.e. neonatal nociceptive priming). The underpinnings of this phenomenon are largely unknown, although macrophages can be epigenetically trained by injury. We found that macrophages are both necessary and partially sufficient to drive neonatal nociceptive priming possibly due to a long-lasting epigenetic remodeling of peripheral macrophages. The p75 neurotrophic factor receptor (NTR) was observed to be an important effector in regulating neonatal nociceptive priming. p75NTR modulates the inflammatory profile and responses of rodent and human macrophages. This pain memory was able to be transferred to a naive host to alter sex-specific pain-related behaviors. This study reveals a novel mechanism by which acute post-surgical pain may transition to chronic pain in children.

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Section: Transplant Of Neonatal "Primed" Bone Marrow Alters Incision-...supporting

confidence: 71%

Section: Discussionmentioning

confidence: 89%

Macrophage epigenetic memories of early life injury drive neonatal nociceptive priming

Dourson

Fadaka

Warshak

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This was connected with changes in inflammation in older rodents compared to younger animals. 100 We found a similar delay following a BMT in female incision at P147 but not in non-BMT males or females. Nevertheless, results reveal that the relatively minor neonatal hindpaw incision injury causes “priming” of the bone marrow and resulted in a female-specific long-lasting phenotype.…”

Section: Discussionmentioning

confidence: 49%

Macrophage memories of early-life injury drive neonatal nociceptive priming

Dourson,

Fadaka,

Warshak

et al. 2024

Cell Reports

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“…To determine the extent of sensory innervation to the ovary, we performed retrograde tracing studies on WT, LKB1 fl/fl , and Na v 1.8 LKB1 females. Fluorogold (Hydroxystilbamidine, Biotium, Cat#80014) was diluted in ddH2O to a 0.4% solution and stored at 4 °C in opaque/black tubes (Black Beauty Microcentrifuge Tubes, Argos Technologies, 1.5mL, Cat#47751-688) (dos Santos et al , 2022; Miller et al , 2021; Mondello et al , 2016; Schmued & Fallon, 1986). All surgical tools were autoclaved before use.…”

Section: Methodsmentioning

confidence: 99%

Sensory neuron LKB1 mediates ovarian and reproductive function

Lenert

Burton

2023

Preprint

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Treatments for reproductive disorders in women primarily consist of hormone replacement therapy, which can have negative health impacts. Bidirectional communication between sensory neurons and innervated organs is an emerging area of interest in tissue physiology with potential relevance for reproductive disorders. Indeed, the metabolic activity of sensory neurons can have profound effects on reproductive phenotypes. To investigate this phenomenon, we utilized a murine model with conditional deletion in sensory neurons of liver kinase B1 (LKB1), a serine/threonine kinase that regulates cellular metabolism. Female mice with this LKB1 deletion (Nav1.8cre;LKB1fl/fl) had significantly more pups per litter compared to wild-type females. Interestingly, the LKB1 genotype of male breeders had no effect on fertility outcomes, thus indicating a female-specific role of sensory neuron metabolism in fertility. LKB1 deletion in sensory neurons resulted in reduced ovarian innervation from dorsal root ganglia neurons and increased follicular turnover compared to littermate controls. In summary, LKB1 expression in peripheral sensory neurons plays an important role in modulating fertility of female mice via ovarian sensory innervation.

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Age and sex drive differential behavioral and neuroimmune phenotypes during postoperative pain

Cited by 7 publications

References 94 publications

Macrophage epigenetic memories of early life injury drive neonatal nociceptive priming

Macrophage epigenetic memories of early life injury drive neonatal nociceptive priming

Macrophage memories of early-life injury drive neonatal nociceptive priming

Sensory neuron LKB1 mediates ovarian and reproductive function

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